PROJECT ABSTRACT Candidate: Dr. Brynne Sullivan is an Assistant Professor at the University of Virginia (UVA) with experience in research involving clinical applications of predictive analytics in NICU patients. She is currently supported by an internal mentored career develop award and enrolled in courses to earn a MSc degree in clinical research. Career development plan and goals: The proposed training plan will establish Dr. Sullivan as a clinician- investigator with expertise in predictive analytics to improve diagnosis and outcomes of life-threatening inflammatory illness in very low birth weight infants (VLBW). Training activities during the award period include graduate-level coursework and tutorial in time series analysis, clinical trial methodology and immunology. Research Plan: Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) occur in 20% of VLBW infants and cause significant morbidity and mortality. Early diagnosis and treatment can start the course to recovery before serious injury occurs; therefore, tools to detect the first signs of illness could save lives and improve outcomes for survivors. Physiomarkers, biomarkers and clinical risk markers of LOS and NEC exist, currently as separate sources of data. The critical need for making a substantial difference in morbidity and mortality from LOS and NEC is to integrate data to develop tools for earlier diagnosis and treatment. The objective is to develop predictive analytics using clinical, physiomarker and biomarker data and test the hypothesis that integrating these data improves algorithm performance. SPECIFIC AIMS: 1) Develop and validate a Pulse Oximetry Warning Score for early detection of LOS and NEC using patterns in heart rate (HR) and oxygen saturation (SpO2) from a large, multi-center data set and compare performance to predictive models using clinical risk factors; 2) Determine whether biomarkers of immune activation inform risk of imminent LOS and NEC in the context of physiomarker and clinical monitoring; 3) Test feasibility of integrated physiomarker, biomarker and clinical monitoring in a pilot randomized trial to inform next steps of a multi-center trial that will be the focus of an R01 proposal. The proposed research is consistent with the NICHD mission to ensure that all children have the chance to fulfill their potential to live healthy and productive lives free from disease or disability. Mentors: The primary mentor, Randall Moorman, MD, and secondary mentors, Karen Fairchild, MD and William Petri, MD, PhD, have broad and diverse expertise and strong track records in successful completion of NIH-supported studies and in mentoring trainees and junior faculty to become independent investigators. Environment: The UVA Center for Advanced Medical Analytics and Dr. Petri's laboratory will provide the intellectual environment and resources necessary to accomplish the goals of this proposal. The exceptional resources and institutional support at UVA and outstanding multi-disciplinary mentorship team will allow the candidate to achieve her long-term goal of becoming an independent investigator and nationally recognized expert in predictive analytics for life-threatening inflammatory illnesses in premature infants.